Particle Size Reduction and Particle Size Analysis Flashcards
BP definition of powders - tablets and capsules
- Coarse powder
- Medium fine powder: 100-350 micrometers
- fine powder: 50-100 micrometers
BP definition of powders - Suspensions
Very fine powders; 1–50 micrometers
BP definition of powders - Aerosols
Microionised powder: <10 micrometers (majority < 5 micrometers)
BP definition of powders: Nanoparticles
Nanoionised powder: <1 micrometer
How do we get desired particle size we need?
“Bottom up” method:
- start with solution of drug and use controlled crystallisation techniques to grow crystals of the desired range.
“Top Down” method:
- start with large particle size and apply energy to reduce the particle size to the desired range.
How does controlled crystallisation work?
- Dissolve the drug into a “good” solvent
- Add “anti-solvent”
- Drug precipitates
What are the disadvantages of controlled crystallisation?
- easy in theory but difficult in practice
- Toxicity of initial solvent
- Control of crystallisation/precipitation process
Advantages of controlled crystallisation?
Supercritical CO2 technology can be used.
What are the words used interchangeably for “particle size reduction”?
- Comminution
- Grinding
- Microionising
- Pulverisation
- Crushing
- Milling
- Nanoionising
Methods of particle size reduction - cutting
- large materials cut into smaller chunks
- fairly coarse method
- suitable for most materials
- minimum particle size in mm range
- example; exudates to pellets
Methods of particle size reduction - Compression
- force applied to large particle above or side against a fixed surface
- particle is trapped between two surfaces
- may include some shear forces
- large particle fracture gives to smaller particles
- fairly coarse method
- minimum particle size in mm range
- example: coarse powders to less coarse powders
Methods of particle size reduction - Impact
- Force applied to large particle by device, e.g hammer or other particle
- particle isn’t necessarily in contact with another solid surface
- The large particle fractures to give smaller particles
- Can be used with wide range of particle sizes
- minimum particle size in 10 micrometers range
- example - coarse powders to finer powders
Methods of particle size reduction - attrition
- Force applied to surface of larger particle to erode bit by bit
- large particle erodes away to give lots of smaller particles and reduces itself in size
- minimum particle size in micrometer range
- example - medium fine to ultra fine particles
Methods of particle size reduction - Dry Milling
- Mixture of impact and attrition
- Particles treated in dry state, usually added moving milling material, e.g large balls
- particles and milling material both move
- milling balls are tougher than particles
Dry milling - further
- usually small scale process
- difficult to obtain particle sizes below 1 micrometer
- surface energy accumulation leads to clumping
- energy input may lead to conversion of polymorphic form, amorphisation, chemical degradation
- can be run chilled (cryo-mill) to reduce these changes
- e.g - medium fine to ultra fine particles, usually drug
